HAEM5:Primary cutaneous gamma/delta T-cell lymphoma: Difference between revisions
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|Activating missense (e.g., N642H) → constitutive STAT5B signalling (JAK/STAT pathway) | |Activating missense (e.g., N642H) → constitutive STAT5B signalling (JAK/STAT pathway) | ||
|Oncogene | |Oncogene | ||
|Recurrent (5‑20%) (JAK/STAT mutations ~21% | |Recurrent (5‑20%) (JAK/STAT mutations ~21%) | ||
|T / P | |T / P | ||
|No | |No | ||
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|Activating missense → constitutive STAT3 signalling (JAK/STAT cascade) | |Activating missense → constitutive STAT3 signalling (JAK/STAT cascade) | ||
|Oncogene | |Oncogene | ||
|Rare (<5%) to Recurrent (~5‑20% | |Rare (<5%) to Recurrent (~5‑20%) | ||
|T / P | |T / P | ||
|No | |No | ||
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|Activating mutation (e.g., R657W) → JAK3 tyrosine kinase activation (JAK/STAT pathway) | |Activating mutation (e.g., R657W) → JAK3 tyrosine kinase activation (JAK/STAT pathway) | ||
|Oncogene | |Oncogene | ||
|Rare (<5% | |Rare (<5%) | ||
|T | |T | ||
|No | |No | ||
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|Activating hotspot mutations (e.g., G12D, Q61H) → RAS/MAPK pathway activation | |Activating hotspot mutations (e.g., G12D, Q61H) → RAS/MAPK pathway activation | ||
|Oncogene | |Oncogene | ||
|Recurrent (5‑20% | |Recurrent (5‑20%) | ||
|T / P | |T / P | ||
|No | |No | ||
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|Activating hotspot mutation → RAS/MAPK pathway activation | |Activating hotspot mutation → RAS/MAPK pathway activation | ||
|Oncogene | |Oncogene | ||
|Rare (<5%) to Recurrent (~5‑20% | |Rare (<5%) to Recurrent (~5‑20%) | ||
|T / P | |T / P | ||
|No | |No | ||
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|Activating missense mutation (e.g., P74L) → MYC pathway up‑regulation | |Activating missense mutation (e.g., P74L) → MYC pathway up‑regulation | ||
|Oncogene | |Oncogene | ||
|Rare (<5% | |Rare (<5%) | ||
|P / T | |P / T | ||
|No | |No | ||
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|Activating mutation (e.g., G34R) → MYCN pathway activation | |Activating mutation (e.g., G34R) → MYCN pathway activation | ||
|Oncogene | |Oncogene | ||
|Rare (<5% | |Rare (<5%) | ||
|P / T | |P / T | ||
|No | |No | ||
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|Copy number loss or gain → altered gene dosage of tumour suppressors/oncogenes | |Copy number loss or gain → altered gene dosage of tumour suppressors/oncogenes | ||
|Other / chromosomal alteration | |Other / chromosomal alteration | ||
|Recurrent (5‑20%) (9p del ~22%, 18q del ~22%; 1q/7q/15q gains ~33‑39% | |Recurrent (5‑20%) (9p del ~22%, 18q del ~22%; 1q/7q/15q gains ~33‑39%) | ||
|D / P | |D / P | ||
|No | |No | ||
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|'''Fusion: FYN :: (probable partner TRAF3IP2)''' | |'''Fusion: FYN :: (probable partner TRAF3IP2)''' | ||
|TRAF3IP2 | |TRAF3IP2 | ||
|Structural alteration – deletion/exon8 deletion → (in other T‑cell lymphomas) FYN::TRAF3IP2 fusion leading to SRC‑family kinase activation; in this PCGDTCL case FYN exon8 deletion noted | |Structural alteration – deletion/exon8 deletion → (in other T‑cell lymphomas) FYN::TRAF3IP2 fusion leading to SRC‑family kinase activation; in this PCGDTCL case FYN exon8 deletion noted | ||
|Oncogene / Other | |Oncogene / Other | ||
|Rare (<5%) (single case reported) | |Rare (<5%) (single case reported) | ||
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|Fusion → juxtaposition of dimerization domain of PCM1 with kinase domain of JAK2 → constitutive JAK2 activation | |Fusion → juxtaposition of dimerization domain of PCM1 with kinase domain of JAK2 → constitutive JAK2 activation | ||
|Oncogene | |Oncogene | ||
|Rare (<5%) (single documented PCGDTCL case | |Rare (<5%) (single documented PCGDTCL case) | ||
|T | |T | ||
|No | |No | ||
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|Fusion → truncation/overexpression of ΔNp63 form → oncogenic p63 signalling | |Fusion → truncation/overexpression of ΔNp63 form → oncogenic p63 signalling | ||
|Oncogene / Other | |Oncogene / Other | ||
|Rare (<5%) (same single case) ( | |Rare (<5%) (same single case) ( | ||
|P / T | |P / T | ||
|No | |No | ||
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|'''Frequent deletions of 9p21.3 (CDKN2A region)''' (part of the SCNV pattern) <ref name=":0" /> | |'''Frequent deletions of 9p21.3 (CDKN2A region)''' (part of the SCNV pattern) <ref name=":0" /> | ||
|Loss of CDKN2A/p14^ARF leads to cell‑cycle deregulation, loss of tumour suppressor control: a hallmark of many aggressive lymphomas | |Loss of CDKN2A/p14^ARF leads to cell‑cycle deregulation, loss of tumour suppressor control: a hallmark of many aggressive lymphomas | ||
|'''Common''' (>20%) (approx 61% of cases | |'''Common''' (>20%) (approx 61% of cases) | ||
|P | |P | ||
|No | |No | ||
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|'''Multiple gains of oncogenic arms (e.g., 1q, 7q, 15q) and corresponding losses (eg 18q)''' <ref name=":0" /> | |'''Multiple gains of oncogenic arms (e.g., 1q, 7q, 15q) and corresponding losses (eg 18q)''' <ref name=":0" /> | ||
|Gains may increase dosage of oncogenes; losses may reduce tumour suppressor dosage—together contributing to malignant phenotype | |Gains may increase dosage of oncogenes; losses may reduce tumour suppressor dosage—together contributing to malignant phenotype | ||
|'''Recurrent''' (5‑20%) for specific arm‑level changes (e.g., 1q gain ~33%, 7q ~39%, 15q ~33% | |'''Recurrent''' (5‑20%) for specific arm‑level changes (e.g., 1q gain ~33%, 7q ~39%, 15q ~33%) | ||
|P | |P | ||
|No | |No | ||
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|T / P: Therapeutic potential (JAK/STAT inhibition); Prognostic implication (pathway addiction/resistance) | |T / P: Therapeutic potential (JAK/STAT inhibition); Prognostic implication (pathway addiction/resistance) | ||
|No | |No | ||
|Mutant STAT5B (especially N642H) shown to induce T‑cell neoplasia in models; in PCGDTCL JAK/STAT addiction shown clinically | |Mutant STAT5B (especially N642H) shown to induce T‑cell neoplasia in models; in PCGDTCL JAK/STAT addiction shown clinically <ref name=":1" /><ref name=":3">{{Cite journal|last=Zhang|first=Yue|last2=Yescas|first2=Julia A.|last3=Tefft|first3=Kristy|last4=Ng|first4=Spencer|last5=Qiu|first5=Kevin|last6=Wang|first6=Erica B.|last7=Akhtar|first7=Shifa|last8=Walker|first8=Addie|last9=Welborn|first9=Macartney|date=2025-04-15|title=Addiction of primary cutaneous γδ T cell lymphomas to JAK/STAT signaling|url=https://pubmed.ncbi.nlm.nih.gov/40231467|journal=The Journal of Clinical Investigation|volume=135|issue=8|pages=e180417|doi=10.1172/JCI180417|issn=1558-8238|pmc=11996904|pmid=40231467}}</ref> | ||
|- | |- | ||
|'''STAT3''' | |'''STAT3''' | ||
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|T / P | |T / P | ||
|No | |No | ||
|Less frequent than STAT5B in PCGDTCL; part of JAK/STAT | |Less frequent than STAT5B in PCGDTCL; part of JAK/STAT pathway involvement<ref name=":0" /><ref name=":1" /> | ||
|- | |- | ||
|'''JAK3''' | |'''JAK3''' | ||
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|T | |T | ||
|No | |No | ||
|Supports JAK/STAT involvement; one case report showed response to JAK inhibition | |Supports JAK/STAT involvement; one case report showed response to JAK inhibition<ref name=":3" /> | ||
|- | |- | ||
|'''KRAS''' | |'''KRAS''' | ||
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|T / P | |T / P | ||
|No | |No | ||
|MAPK pathway appears relevant; patients with MAPK‑pathway driver mutations had worse survival in the cohort | |MAPK pathway appears relevant; patients with MAPK‑pathway driver mutations had worse survival in the cohort<ref name=":0" /> | ||
|- | |- | ||
|'''NRAS''' | |'''NRAS''' | ||
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|T | |T | ||
|No | |No | ||
|Also in MAPK pathway; limited data in PCGDTCL | |Also in MAPK pathway; limited data in PCGDTCL<ref name=":0" /><ref name=":1" /> | ||
|- | |- | ||
|'''MYC''' | |'''MYC''' | ||